When fertile hen's eggs are switched from a 21% oxygen to a 60% oxygen environment on the fifteenth day of incubation, embryonic growth and 02 consumption are greater for the next three days than controls maintained at 21% 02. The opposite effects occur when the 02 concentration in the incubator is switched from 21% to 15% on the 15th day; embryonic growth slows and embryonic 02 consumption falls. These data suggest that oxygen availability normally limits the growth of the chick embryo beginning on the 15th day of incubation. We propose to investigate the mechanism by which 02 influences embryonic growth and metabolism. We will explore the possibility that 02 modifies growth through its action on the production of known anabolic hormones by measuring plasma concentrations of thyroid hormones, insulin, avian growth hormone, and avian insulin-like growth factors in circulating blood, taking samples from embryos in 15%, 21% and 60% 02. We will also add plasma from each of these experimental groups to chick embryo fibroblasts in culture and measure the rates of cell division, protein synthesis, and DNA synthesis. We will evaluate the possibility that 02 acts directly at the cellular level by comparing the biochemical characteristics of chick embryo tissues from 15% 02, 21% 02 and 60% 02 embryos with data obtained on cultured cells grown in media with different oxygen tensions. We will also attempt to develop the fetus of the guinea pig as a mammalian model of hyperoxic growth stimulation. We will increase 02 availability to the guines pig fetus beginning on day 53 of pregnancy by increasing maternal blood 02 capacity or decreasing maternal blood 02 affinity, or by a combination of these two procedures, measuring the effects by comparing fetal weight and the wet and dry weights of selected fetal organs with those from controls that have been cross-transfused without altering blood 02 affinity or capacity. Measurements of placental blood flow in experimental and control animals will be made at 63 days so the effects of changing blood respiratory characteristics on the blood flow to maternal organs, including placentas, can be evaluated. If 02 availability (the product of arterial 02 content and placental blood flow) is not increased by these changes in maternal blood, we will increase the hematocrit of one fetus, comparing its growth with controls. If one of these interventions evokes fetal growth acceleration, we will begin to compare 02-induced growth acceleration in the guinea pig with 02-induced growth acceleration of the chick embryo.